Hearing loss - a very common condition affecting hundreds of millions of people globally - has substantial adverse impact on human health and quality of life, and is associated with a wide variety of adverse social, psychological, and occupational consequences. It also has a substantial impact on learning outcomes and intellectual development in children. A potentially important but not well-researched cause of hearing loss is exposure to environmental contaminants, and in particular heavy metals. A limited but highly suggestive body of research suggests that exposures to lead (Pb) and cadmium (Cd) - both common environmental contaminants in the United States and worldwide - may be associated with an increased risk of hearing loss. However, no causal link has yet been established between exposure to heavy metals and hearing loss. Moreover, adverse effects of environmental contaminants (e.g., organic solvents) can be aggravated by concurrent exposure to noise which is present in many environments contaminated with heavy metals. Such interactions have not been explored for Pb or Cd. The proposed study will evaluate and quantify, in a well- understood animal model (CBA/J mice), the relationship between Pb and Cd exposure and hearing damage. The first hypothesis is that exposure to Pb and Cd will be associated with a risk of hearing and vestibular damage. To evaluate this hypothesis we will expose groups of young mice to varying doses of Pb or Cd in their drinking water for a period of 8 weeks, achieving serum levels commonly found in humans in contaminated areas. We will quantitatively evaluate animals' auditory thresholds at baseline and at the midpoint and end of the exposure period via Auditory Brainstem Response (ABR) and Distortion Product Otoacoustic Emissions (DPOAEs). We will also evaluate vestibular function at the same time points. At the conclusion of the study we will conduct cochlear hair cell counts to enumerate cochlear damage, and will analyze Pb levels in the ossicles and other selected bones as an additional measure of Pb exposure. The second hypothesis is that a combination of noise and Pb or Cd will result in a greater hearing loss than exposure to noise or metals alone. To evaluate synergistic or additive effects of these agents we will measure auditory deficits resulting from noise exposure alone or in combinations with Pb or Cd. This project addresses two of NIDCD's focus areas (hearing loss and balance); improvements in health in these areas, such as those that might ultimately results from the proposed work, are also goals of the Healthy People 2020 program. Successful collection of pilot data in the proposed study will result in a subsequent R01 application to NIDCD. The results of this study may help guide future public health interventions designed to reduce the burden of hearing loss through reductions in environmental exposures to heavy metals.